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Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer

Neuronal nerve processes in the tumor microenvironment were highlighted recently. However, the origin of intra-tumoral nerves remains poorly known, in part because of technical difficulties in tracing nerve fibers via conventional histological preparations. Here, we employ three-dimensional (3D) ima...

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Autores principales: Guillot, Jérémy, Dominici, Chloé, Lucchesi, Adrien, Nguyen, Huyen Thi Trang, Puget, Angélique, Hocine, Mélanie, Rangel-Sosa, Martha M., Simic, Milesa, Nigri, Jérémy, Guillaumond, Fabienne, Bigonnet, Martin, Dusetti, Nelson, Perrot, Jimmy, Lopez, Jonathan, Etzerodt, Anders, Lawrence, Toby, Pudlo, Pierre, Hubert, Florence, Scoazec, Jean-Yves, van de Pavert, Serge A., Tomasini, Richard, Chauvet, Sophie, Mann, Fanny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007988/
https://www.ncbi.nlm.nih.gov/pubmed/35418199
http://dx.doi.org/10.1038/s41467-022-29659-w
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author Guillot, Jérémy
Dominici, Chloé
Lucchesi, Adrien
Nguyen, Huyen Thi Trang
Puget, Angélique
Hocine, Mélanie
Rangel-Sosa, Martha M.
Simic, Milesa
Nigri, Jérémy
Guillaumond, Fabienne
Bigonnet, Martin
Dusetti, Nelson
Perrot, Jimmy
Lopez, Jonathan
Etzerodt, Anders
Lawrence, Toby
Pudlo, Pierre
Hubert, Florence
Scoazec, Jean-Yves
van de Pavert, Serge A.
Tomasini, Richard
Chauvet, Sophie
Mann, Fanny
author_facet Guillot, Jérémy
Dominici, Chloé
Lucchesi, Adrien
Nguyen, Huyen Thi Trang
Puget, Angélique
Hocine, Mélanie
Rangel-Sosa, Martha M.
Simic, Milesa
Nigri, Jérémy
Guillaumond, Fabienne
Bigonnet, Martin
Dusetti, Nelson
Perrot, Jimmy
Lopez, Jonathan
Etzerodt, Anders
Lawrence, Toby
Pudlo, Pierre
Hubert, Florence
Scoazec, Jean-Yves
van de Pavert, Serge A.
Tomasini, Richard
Chauvet, Sophie
Mann, Fanny
author_sort Guillot, Jérémy
collection PubMed
description Neuronal nerve processes in the tumor microenvironment were highlighted recently. However, the origin of intra-tumoral nerves remains poorly known, in part because of technical difficulties in tracing nerve fibers via conventional histological preparations. Here, we employ three-dimensional (3D) imaging of cleared tissues for a comprehensive analysis of sympathetic innervation in a murine model of pancreatic ductal adenocarcinoma (PDAC). Our results support two independent, but coexisting, mechanisms: passive engulfment of pre-existing sympathetic nerves within tumors plus an active, localized sprouting of axon terminals into non-neoplastic lesions and tumor periphery. Ablation of the innervating sympathetic nerves increases tumor growth and spread. This effect is explained by the observation that sympathectomy increases intratumoral CD163(+) macrophage numbers, which contribute to the worse outcome. Altogether, our findings provide insights into the mechanisms by which the sympathetic nervous system exerts cancer-protective properties in a mouse model of PDAC.
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spelling pubmed-90079882022-04-27 Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer Guillot, Jérémy Dominici, Chloé Lucchesi, Adrien Nguyen, Huyen Thi Trang Puget, Angélique Hocine, Mélanie Rangel-Sosa, Martha M. Simic, Milesa Nigri, Jérémy Guillaumond, Fabienne Bigonnet, Martin Dusetti, Nelson Perrot, Jimmy Lopez, Jonathan Etzerodt, Anders Lawrence, Toby Pudlo, Pierre Hubert, Florence Scoazec, Jean-Yves van de Pavert, Serge A. Tomasini, Richard Chauvet, Sophie Mann, Fanny Nat Commun Article Neuronal nerve processes in the tumor microenvironment were highlighted recently. However, the origin of intra-tumoral nerves remains poorly known, in part because of technical difficulties in tracing nerve fibers via conventional histological preparations. Here, we employ three-dimensional (3D) imaging of cleared tissues for a comprehensive analysis of sympathetic innervation in a murine model of pancreatic ductal adenocarcinoma (PDAC). Our results support two independent, but coexisting, mechanisms: passive engulfment of pre-existing sympathetic nerves within tumors plus an active, localized sprouting of axon terminals into non-neoplastic lesions and tumor periphery. Ablation of the innervating sympathetic nerves increases tumor growth and spread. This effect is explained by the observation that sympathectomy increases intratumoral CD163(+) macrophage numbers, which contribute to the worse outcome. Altogether, our findings provide insights into the mechanisms by which the sympathetic nervous system exerts cancer-protective properties in a mouse model of PDAC. Nature Publishing Group UK 2022-04-13 /pmc/articles/PMC9007988/ /pubmed/35418199 http://dx.doi.org/10.1038/s41467-022-29659-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Guillot, Jérémy
Dominici, Chloé
Lucchesi, Adrien
Nguyen, Huyen Thi Trang
Puget, Angélique
Hocine, Mélanie
Rangel-Sosa, Martha M.
Simic, Milesa
Nigri, Jérémy
Guillaumond, Fabienne
Bigonnet, Martin
Dusetti, Nelson
Perrot, Jimmy
Lopez, Jonathan
Etzerodt, Anders
Lawrence, Toby
Pudlo, Pierre
Hubert, Florence
Scoazec, Jean-Yves
van de Pavert, Serge A.
Tomasini, Richard
Chauvet, Sophie
Mann, Fanny
Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer
title Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer
title_full Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer
title_fullStr Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer
title_full_unstemmed Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer
title_short Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer
title_sort sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007988/
https://www.ncbi.nlm.nih.gov/pubmed/35418199
http://dx.doi.org/10.1038/s41467-022-29659-w
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